The study will compare how well transplanted kidneys work and the response of people's immune systems as tacrolimus, a calcineurin inhibitor (CNI), is withdrawn. In addition, this research study will evaluate whether reducing immunosuppression can decrease some of these side effects while still preventing rejection of the kidney.

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

Percentage of Participants With Incremental IF/A Scores >2 at 24 Months Post-Randomization [ Time Frame: IF/TA scores on protocol biopsies obtained at 24 months post-randomization will be compared to those obtained at the time of implantation for this measurement. ] [ Designated as safety issue: No ]

The investigators were not able to assess this outcome, the effect of the intervention on interstitial fibrosis/tubular atrophy (IF/TA; on a 2-year graft biopsy) due to the study's premature termination by the Data Safety Monitoring Board (DSMB) because of absence of equipoise on the basis of predetermined stopping rules.

Acute renal allograft rejection is defined as histological reading of borderline or greater determined by the local pathology laboratory. Participants suspected of having a rejection episode on the basis of clinical signs, symptoms, or on the basis of laboratory tests, had a renal ultrasound and underwent a renal transplant biopsy. Any detection of acute cellular rejection or acute humoral rejection resulted in participants in the 'Randomized to Tacrolimus Withdrawal' group to be restarted on tacrolimus and followed per the reduced follow-up schedule of events.

Donor specific antibodies are antibodies that are directed against antigens expressed on donor organs. These antibodies can result in an immune attack on the transplanted organ, increasing risk of graft loss and/or rejection.

This endpoint was unable to be analyzed because the study was terminated early after stopping rules were met.

Percentage of Participants in the Experimental Arm Off Tacrolimus [ Time Frame: 18 months post-randomization ] [ Designated as safety issue: No ]

Participants in the 'Randomized to Tacrolimus Withdrawal' group were considered fully withdrawn once they no longer received any doses of tacrolimus. Participants met this endpoint if they did not resume taking tacrolimus as of 18 months post randomization with stable allograft function and without rejection of donor-specific antibodies.

Recipients of living-donor kidney allografts are given induction therapy with rabbit antithymocyte globulin (RATG, Thymoglobulin®) and treated with a standard immunosuppressive regimen of mycophenolate mofetil (MMF), prednisone and tacrolimus.Subjects without any clinical acute rejection (AR) in the first 6 months, without borderline or acute rejection on the 6 month biopsy, and without donor-specific antibody (DSA) at anytime, including the 6 month test are randomized (2:1) to tacrolimus (CNI) withdrawal.

Drug: Tacrolimus (CNI) Withdrawal

Recipients of living-donor kidney allografts are given induction therapy with rabbit antithymocyte globulin (RATG, Thymoglobulin®) and treated with a regimen of mycophenolate mofetil (MMF), prednisone and tacrolimus.

Subjects without any clinical acute rejection (AR) in the first 6 months, without borderline or acute rejection on the 6 month biopsy, and without donor-specific antibody (DSA) at anytime, including the 6 month test will be randomized (2:1) to tacrolimus (CNI) withdrawal.

Other Names:

ATG Induction,Tacrolimus (CNI), MMF and Prednisone, Followed by CNI Withdrawal

rabbit antithymocyte globulin (RATG)

Thymoglobulin®

calcineurin inhibitor (CNI)

mycophenolate mofetil

CellCept®

Drug: Standard Immunosuppressive Therapy

Recipients of living-donor kidney allografts are given induction therapy with rabbit antithymocyte globulin (RATG, Thymoglobulin®) and treated with a regimen of mycophenolate mofetil (MMF), prednisone and tacrolimus.

Recipients of living-donor kidney allografts are given induction therapy with rabbit antithymocyte globulin (RATG, Thymoglobulin®) and treated with a standard immunosuppressive regimen of mycophenolate mofetil (MMF), prednisone and tacrolimus. Tacrolimus (CNI) withdrawal does not occur.

Drug: Standard Immunosuppressive Therapy

Recipients of living-donor kidney allografts are given induction therapy with rabbit antithymocyte globulin (RATG, Thymoglobulin®) and treated with a regimen of mycophenolate mofetil (MMF), prednisone and tacrolimus.

Other Names:

ATG induction,Tacrolimus (CNI), MMF and Prednisone

rabbit antithymocyte globulin (RATG)

Thymoglobulin®

calcineurin inhibitor (CNI)

mycophenolate mofetil

CellCept®

Detailed Description:

Kidney transplantation is a treatment option for people with kidney disease. However, there is still much to learn about how to best care for the transplanted kidney and keep it functioning for a long time. Transplant recipients take immunosuppression (anti-rejection) drugs to prevent their body from rejecting the new kidney. These drugs are used to prevent the immune system from attacking the transplanted kidney. All anti-rejection medications have unwanted side effects. The purpose of this study is to evaluate the safety of slowly removing tacrolimus, a CNI.

Eligibility

Ages Eligible for Study:

18 Years and older (Adult, Senior)

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

INCLUSION CRITERIA -

Initial Enrollment/Screening: Patients who meet all of the following criteria are eligible for enrollment as study subjects:

Subject must be able to understand and provide written informed consent;

Peak flow-based PRAs for class I and class II <30%(performed by local center);

Current (within 8 weeks prior to transplantation) flow-based PRAs for class I and class II <30% (performed by local center);

No donor specific antibody by flow solid phase method on the peak PRA serum (if serum available), or on the current PRA serum (within 8 weeks prior to transplantation) performed by central core laboratory. If the sera for the peak PRA is not available, then only the current PRA serum will be tested;

Negative T-cell and B-cell crossmatch by flow cytometry (performed by local center);

Female subjects of childbearing potential must have a negative pregnancy test (urine or serum) upon study entry;

Female and male subjects with reproductive potential must agree to use FDA approved methods of birth control while participating in the study.

Inclusion Criteria for Randomization:

Participants who meet all of the following criteria are eligible for randomization:

No history of acute rejection episodes;

The pre-randomization protocol biopsy should confirm no rejection, including borderline rejection (based on the central pathology read);

Participants who meet any of these criteria are not eligible for enrollment as study subjects:

Recipient of multiple organ transplants;

Prior history of organ transplantation;

Deceased-donor source;

Any condition that would preclude protocol biopsies;

HLA identical recipients;

Currently breast-feeding or plans to become pregnant during the timeframe of the study follow up period;

Any condition that, in the opinion of the investigator, would interfere with the subject's ability to comply with study requirements;

Inability or unwillingness to comply with study protocol;

Use of investigational drugs within 4 weeks of study entry and for the duration of the study;

Recent recipient of any licensed or investigational live attenuated vaccine(s) within two months of prior to study entry.

Exclusion Criteria for Randomization:

Participants who meet any of these criteria are not eligible for randomization:

Subjects who receive less than 4.5mg/kg of Rabbit ATG (Thymoglobulin®) induction therapy;

Subjects who test positive for BKV by PCR in the blood at 6 months post-transplant;

Any condition that would preclude protocol biopsies;

Currently breast-feeding or plans to become pregnant during the timeframe of the study follow up period;

Any condition that, in the opinion of the investigator, would interfere with the subject's ability to comply with study requirements;

Inability or unwillingness of a subject to give written informed consent or comply with study protocol;

Use of investigational drugs within 4 weeks of study entry and for the duration of the study;

Subjects who receive less than 1500 mg daily of Mycophenolate Mofetil (CellCept®) or equivalent.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01517984